Tan Hao-Yang, Sust Steven, Buckholtz Joshua W, Mattay Venkata S, Meyer-Lindenberg Andreas, Egan Michael F, Weinberger Daniel R, Callicott Joseph H
Unit on Functional MRI, Clinical Brain Disorders Branch, Intramural Research Program, National Institute of Mental Health, 10 Center Dr., Rm 4C-216, MSC 1364, Bethesda, MD 20892-1364, USA.
Am J Psychiatry. 2006 Nov;163(11):1969-77. doi: 10.1176/ajp.2006.163.11.1969.
It has been suggested that in healthy persons higher-order cognitive processing engaged by incremental working memory load hierarchically employs more dorsal than ventral prefrontal resources in healthy individuals. Given that working memory performance is impaired in schizophrenia, especially at higher executive loads, the authors investigated how this prefrontal functional organization might be altered in disease, independent of performance deficits.
Using N-back working memory functional magnetic resonance imaging (fMRI) data, the authors studied 15 patients with schizophrenia and 26 healthy comparison subjects. Subgroups based on median performance accuracy at 2-back were analyzed; high performers included eight schizophrenia patients and 14 comparison subjects, and low performers included seven patients and 12 comparison subjects.
High-performing but not low-performing comparison subjects responded to incremental working memory executive load with disproportionately greater dorsal but not ventral prefrontal cortex activation, which also predicted performance accuracy. In the high- and low-performing patient groups, incremental working memory load caused a disproportionate increase in ventral but not dorsal prefrontal cortex activation relative to the respective comparison group, which also correlated with accuracy. Functional connectivity between the ventral prefrontal cortex and posterior parietal cortex was relatively greater in patients, whereas comparison subjects had greater functional connectivity between the dorsal prefrontal cortex and posterior parietal cortex.
The hierarchical organization of the prefrontal cortex may be compromised in schizophrenia, resulting in loss of functional specialization and integration at the dorsal prefrontal cortex and in compensatory activation from the ventral prefrontal cortex, which may ultimately affect working memory and executive cognition.
有人提出，在健康个体中，由递增的工作记忆负荷所引发的高阶认知加工在层级上更多地利用背侧而非腹侧前额叶资源。鉴于精神分裂症患者的工作记忆表现受损，尤其是在较高执行负荷时，作者研究了这种前额叶功能组织在疾病中可能如何改变，而不考虑表现缺陷。
作者使用N-back工作记忆功能磁共振成像（fMRI）数据，研究了15名精神分裂症患者和26名健康对照者。根据2-back任务的中位表现准确性进行亚组分析；表现优秀者包括8名精神分裂症患者和14名对照者，表现不佳者包括7名患者和12名对照者。
表现优秀而非表现不佳的对照者对递增的工作记忆执行负荷的反应是，背侧前额叶皮质激活不成比例地增加，而腹侧前额叶皮质激活没有增加，这也预测了表现准确性。在表现优秀和表现不佳的患者组中，相对于各自的对照组，递增的工作记忆负荷导致腹侧前额叶皮质激活不成比例地增加，而背侧前额叶皮质激活没有增加，这也与准确性相关。患者腹侧前额叶皮质与顶叶后皮质之间的功能连接相对更强，而对照者背侧前额叶皮质与顶叶后皮质之间的功能连接更强。
前额叶皮质的层级组织在精神分裂症中可能受到损害，导致背侧前额叶皮质功能特化和整合丧失，以及腹侧前额叶皮质的代偿性激活，这最终可能影响工作记忆和执行认知。
